N-(2 - dialkylaminoalkylene)-esters of fluoroalkoxy-substituted aryl carboxylic acid and salts thereof

ABSTRACT

N- (2 - DIALKYLAMINOALKYLENE) CARBOXYLIC ESTERS OF POLYFLUORALKOXY-SUBSTITUTED AROMATIC ACIDS. ALSO INCLUDED ARE PHARMACEUTICALLY ACCEPTABLE SALTS OF THESE COMPOUNDS. THESE COMPOUNDS HAVE VALUABLE LOCAL ANESTHETIC ACTIVITY.

United States Patent Oflice 3,655,728 Patented Apr. 11, 1972 3,655,728 N-(2 DIALKYLAMINOALKYLENE)-ESTERS OF FLUOROALKOXY-SUBSTITUTED ARYL CAR- BOXYLIC ACID AND SALTS THEREOF Arthur Mendel, Vadnais Heights, Minn., assignor to Riker Laboratories, Inc., N orthridge, Calif. No Drawing. Filed July 22, 1970, Ser. No. 57,351 Int. Cl. C07c 69/76 U.S. Cl. 260-473 R 9 Claims ABSTRACT OF THE DISCLOSURE N (2 dialkylaminoalkylene)carboxylic esters of polyfluoroalkoxy-substituted aromatic acids. Also included are pharmaceutically acceptable salts of these compounds. These compounds have valuable local anesthetic activity.

DETAILED DESCRIPTION The present invention relates to N (2 dialkylaminoalkylene)esters, which are also sometimes referred to herein as ,8 dialkylaminoalkyl esters, of polyfluoroalkoxy-substituted aromatic acids, and to salts thereof with pharmaceutically acceptable acids. These compounds have valuable local anesthetic activity.

A preferred class of compounds of the invention are those having the formula:

wherein R and R' are lower alkyl groups of one to three carbon atoms, Q is hydrogen or a lower alkyl group of one to three carbon atoms, Ar is an aromatic group containing from six to ten carbon atoms, R; is a fluorocarbon group having from 1 to 3 carbon atoms and n is 1-4; and pharmaceutically acceptable salts thereof. The complete fluorocarbon group (Rf) can be a fully or partially fluorinated al-kyl group having a straight or branched structure. There can be no more than one hydrogen atom on any carbon atom and two carbon atoms in the R; group can be linked together by an oxygen atom. Thus, in addition to the optional oxygen atom, R; can contain only carbon, fiuorine and hydrogen. A preferred class of the compounds of the invention is made up of those compounds in which R group is trifiuoromethyl. The R groups can be, but need not be, the same in any particular compound.

A particularly preferred subclass of the compounds are those in which Ar is a condensed ring system containing ten carbon atoms (a naphthalene nucleus) and n is 1. These compounds are particularly desirable local anesthetics having activity of long duration. A second preferred subclass consists of those in which Ar is a sixmembered aromatic carbocycle (a benzene nucleus) and n is 2.

The compounds of the invention can be used in the ester form directly but are also suitably used in the form of pharmaceutically acceptable salts thereof, especially as soluble hydrochlorides or sulfates. Other such salts include combinations with hydrobromic acid, sulfamic acid, phosphoric acid, methanesulfonic acid, benzene sulfonic acid, ethane disulfonic acid, acetic acid, citric acid, malic acid, succinic acid, maleic acid, fumaric acid, tartaric acid and benzylic acid.

The compounds of the invention have not only a high degree of activity compared to other local anesthetics, but, in some cases, the duration of that activity is surprisingly great. They may be administered by topical application to produce surface anesthesia and used to relieve itching, burning and surface pain. They may also be administered by local injection for surgical procedures. When they are administered topically, the compounds may be administered from aqueous solutions, in pharmaceutical cream or salve bases, etc. The compounds can be conveniently injected in solutions, e.g. in aqueous or saline solutions.

Both the degree and the duration of local anesthetic activity can be conveniently demonstrated by means of a corneal reflex test utilizing rabbits as test animals. In this test the anesthetic solution is instilled in the conjunctival sac of the rabbit eye. The corneal reflex is then tested for insensibility by drawing a thread across the pupil and observing any reflex action.

The results of tests run using this procedure to compare the eflicacy of a typical compound of the invention (5 diethylaminoethyl 1 (2,2,2 trifluoroethoxy) 2- naphthoate hydrochloride) and the widely used local anesthetic procaine are presented in the two following tables. The test compound of the invention and the procaine are both used in dilute aqueous solutions. Two to four drops of the solution are placed in the test site and held in situ for one minute. The corneal reflex is tested six times at each of the various elapsed times indicated after administration of the test compound.

TABLE I.PERCENT INHIBITION OF CORNEAL REFLEX Time (minutes) Test compound l 1 Tested from a 1 percent aqueous solution. 1 Test discontinued.

TABLE II.PEROENT INHIBITION OF CORNEAL REFLEX Time Test com- Pro- (minutes) pound 1 caine 1 1 Tested from a 0.1 percent aqueous solution. 2 Tested from a 1 percent aqueous solution.

Other compounds showing excellent long term local anesthetic activity are p-diethylaminoethyl 3-(2,2,2-trifluoroethoxy)-2-naphthoate hydrochloride and fl-diethylaminoethyl-2,5 di-(2,2,2-trifiuoroethoxy) benzoate hydro chloride.

The compounds of Formula I can be produced by converting a hydroxyaryl ester of the formula:

carbonate in an inert solvent such as acetone. The resulting ester (III) is then hydrolyzed to the free acid (III,

R"=H). In these formulas R" is lower alkyl (usually containing not more than about four carbon atoms), CH R: or H, and R Ar and n are as previously defined.

The free acid can be reacted with a p-dialkylaminoalkyl halide or salt thereof, e.g.

( Z(CHQ) NRR' -HCI (wherein Z is halogen such as chlorine or bromine and Q, R and R are as defined above) in the presence of an acid g., 0.06 mole), anhydrous potassium carbonate (13.8 g., 0.1 mole) and acetone (150 m1.) is heated under reflux with efiicient stirring for three days. The product is filtered and the filtrate is concentrated to a small volume. It is diluted with cold water and the resulting precipitate is collected and washed successively with cold dilute sodium hydroxide solution and water. The desired material is recrystallized then from aqueous ethanol to afford white solid, M.P. 61-62 C.

scavenger, such as sodium bicarbonate or potassium bil Analysis-cfllculated m s s s (P carbonate, and an inert solvent, such as toluene or ben- Found (D H, zene, to prepare the fi-dialkylaminoalkyl esters of the invention.

An alternative method for the preparation of com- Example zg gi gfi fi f gi i' pounds of Formula I involves the alcoholysis of an ester y P of the Formula 111 Where is not H with a fi' y A mixture containing 20.2 g. (0.1 mole) of methyl 1- amlnoalkanol Of the fo hydroxy-Z-naphthoate, 29 g. (0.125 mole) of 2,2,2-trifluoroethyl trifluoromethanesulfonate, g. (0.2 mole) (VI) HO(CHQ)2NRR of anhydrous potassium bicarbonate and 200 m1. of dry The starting materials utilized in the preparation of the 20 acetone is refluxed for three days. Acetone is removed by compounds of the invention (compounds of types II, IV, distillation (steam bath). The residue is cooled and diluted V and VI) are well-known to the art. A number of them with water. The resulting white solid is collected by filtraare utilized in the following preparative examples. tion and washed successively with cold dilute sodium hy- The following examples will more fully illustrate the droxide solution and water. The solid is further purified preparation of the compositions of the invention. All temby several recrystallizations from aqueous alcohol folperatures in the examples are given in C. Examples 1-34 lowed by S i b th, 60-75/ 0.2 mm. Hg) to relate to the preparation of intermediate compounds and give white sohd, M.P. 69.5-70.5 C. Examples 35-46 relate to the preparation of compounds ysi- 14 11 303 (percent): C, of the invention. 59.2; H, 3.9; F, 20.0. Found (percent): C, 58.9; H, 4.0;

F, 21.1. Example 2 i methtyl Additional compounds of Formula III, where 'R is not e oxy) enzoa e H and R is CF are prepared according to the procedures A mixture of methyl salicylate (6.4 ml., 7.6 g., 0.05 described in Examples 1 and 2 and are described in Table mole), 2,2,2-trifluoroethyl triifluoromethanesulfonate (13.9 III.

TABLE III Analysis for- Melting Calculated Found point; Example No. Formula (ln 0.) C H F C H F CioHnFaOa 3 0=COCH3 57.5-59 51.3 3.9 24.3 51.2 4.1 25.0

OCHzCFa CHaO OCHZCF;

0 u 0 3H1 1a i2Fu04 a 45.1 3.5 45.0 3.7 l OCHaOH;

OCHZCF! OOHzCF TAB LE III-Continued Analysisfor Melting Calculated Found point Example No. Fonnula (inC.) C H F C H F (IJOCHa OCH CF CF3CH20- (IDOCHs CF3CH 0- OCH:CF3

00H;CF

| OCHQCF;

CF CH 0- 0CH1CF;

C15H1o 12 5 11 (I? 64.8-65.8

([JOCHZCF: 36.2 2.0 45.8 36.1 2.2 46.1

CF CH O- OCH:CF;

I OCH2CF3 014 11 305 12 0 86-87 I] 39.1 2.6 40.0 39.2 2.6 40.3 (KOCH:

CFaCHzO- OCH2CF3 CHzCFa cn n a a 13 O 7777.5 II 59.2 3.9 20.0 59.2 4.2 21.0

COCHa OCHaCFa 1 and 2 but utilizing compounds of Formula IV other than Compounds of Formula III where R" is not H are pre- 2,2,2-trifluoroethyl trifluoromethanesulfonate are shown pared according to the procedures described in Examples 75 in Table IV.

TABLE IV Starting materials Example No. Formula II Formula IV Product, Formula III 14 fl) CFzSOzOCHzCFzCFz (I? ('30 CH; ('30 OH;

OH OCHzCFnCF;

15..-. Same as above. CF3SO2OCH2(CF2)2H (I? (IJOCHz O CH2(CF2)2H 16 OH CFaSO2OCH2(CF2)2CFz (|)CHz(CF2)2CFs COCH2CH3 COCH2CH3 ll ll 0 17 3 CFaSOzO CHaCFzCFa H ('30 CH $0 CH HO OH CFaCFzCHzO- -O CH CF CF;

I I OH O OH2CF2CF3 E l 19.-P t' f 1- 2,2,2- ifl th Exampk 1 Preparation of 2-(2,2,2-trifiuoroethoxy) 35 xamp e gfgggg g tr Home oxy) benzo'c acid 1 A mixture of g. mmoles) of methyl 1-(2,2,2-

Methyl 2-(2,2,2-trifluoroethoxy)-benzoate (8 g., 34.2 l i g ylg' g i 11- g-i l Z n2 l )f0f p0- 5 1 tassium' y roxl e, m. 0 ct ano an O 0 water moles) potassium hydro) e (3 3 g 3 0 mo es) wa is relfluxed for one hour, chilled and acidified. The fluffy ter and alcohol (25 are heated together precipitate is collected, water washed, and air-dried. It is under reflux for 1.5 hours, and distilled until ca. 25 ml. ifi d by recrystallization fi t f hl f and then of distillate is removed. The cooled residue is acidified from aqueous alcohol, M.P. 171.5172 C. (pH 3) and the resulting white solid is collected and re- Analysis-4alculated for 13 9 3 3 (P 45 crystallized (aqueous alcohol) to give fluify white solid, F Found (Percent) Compounds of Formula III where R" is H are ob- A'1alyS1S-Ca1cu1at6d o v s s (P tained from each of the products of Examples 3 through H, 3.2; F, 25.9. Found (percent): C, 48.8; H, 3.3; F, 26.2. 17 by the methods described in detail in Examples 18 and 50 19. Such products where R; is CF are listed in Table V.

TABLE V Analysis for Melting Calculated Found point Example No. Product (in C.) O H F C H F Cn 1 a0a COOH- -0CH2CF 21 ZOO-200.5 49.1 3.2 25.9 49.1 3.5 25. 8

HO 0 O- O CHzC 1";

uHsFaO4 22 (IJOOH 141-143 41.5 2.5 41.9 2.6

0 CH: C F;

O CH C Fl TABLE V--C0ntinued Analysis for Melting Calculated Found point Example No. Product (in C.) C H F O H F 0 CHzC F3 I O CH O F *0 CHzC F3 0 FaCHzO- CF CH O OCH2CF3 -O CHzC F 0 CHzC F CFgCHzO- OCH2CF3 CIBHQFDOE CF CHzO OCH C F 0 CH2C F3 29 (IJOOH 196497 37.5 2.2 41.1 37.5 2.5 41.2

CFgCHeO- 0 01120 F;

l 0 CHzC F3 CwHB a a i C O OH O CHzC F;

Several compounds of Formula 111 where R" is H are pics 18 and 19 where R is other than CF are listed in prepared according to the procedure described in Exam- Table VI.

TABLE VI Example N0. Starting material Product (IJOCHS O CHzC F20 F;

0 01120 F20 Fa TABLE VI-o\n tinflled Example No. Starting material Product:

I O CHACFMII -O OHflOFmI-I 33 (1) (')CH3OF(CF3)z (|)CH:CF(CF3):

C 0 CHzCHa C O OH 0 00 CHa CFaOCFzCHzO- OCHaCFaCOF;

CF OCF CH O- OCHzCFrOCFa O CHQO F90 C F;

O CHzC F C F;

NOTE:

(1) Prepared according to the procedures of Examples 1 and 2 from ethyl 1-hydroxy-2-naphthoate and 1,1-dihydroperfluoroisobutoxy trifluoromethanesulfonate.

2) Prepared according to the procedures of Examples 1 and 2 from methyl 2,4,6-trihydroxybenzoate and 2,2-difluoro-(2-trlfluoromethoxy) ethoxy trifluoromethanesulfonate.

Example 35.Preparation of B-diethylaminoethyl 2,3- di-(2,2,2-trifluoroethoxy)-benzoate hydrochloride A mixture containing 9.55 g. (30 mmoles) of 2,3-di- (2,2,2-trifluoroethoxy)-benzoic acid, 9 g. (90 mmoles) of anhydrous potassium bicarbonate and 100 ml. of toluene is well-stirred and refluxed under a water trap for two hours (most of the water separated within the first hour of reaction). The material is cooled and to it added 5.16 g. (30 mmoles) of p-diethylaminoethyl chloride hydrochloride. This product is refluxed under a water trap with eflicient stirring for one day. Solvent is removed under diminished pressure and the residue is taken up in an ether-water mixture. The organic layer is separated, waterwashed and dried (anhydrous magnesium sulfate). The ethereal solution is filtered and the filtrate is saturated with anhydrous, gaseous hydrogen chloride. The product is protected from moisture and allowed to stand for one day. The resulting white crystals are collected and purified by recrystallization from an absolute alcohol-absolute ether combination. M.P. 7274.5 C.

Analysis.Calculated for C17H22C1FN04 (percent): C, 45.0; H, 4.9; F, 25.1. Found (percent): C, 45.0; H, 5.2; F, 25.2.

Example 36.-Preparation of B-diethylaminoethyl 3,4-di- (2,2,2-trifluoroethoxy) -benzoate maleate Esterification of 3,4 di-(2,2,2-trifluoroethoxy)-benzoic acid (9.55 g., 30 mmoles) in toluene (100 ml.) under a water trap with potassium bicarbonate (9 g., 90 mmoles) and ,B-diethylaminoethyl chloride hydrochloride (5.16 g., 30 mmoles) followed by work up is conducted as described in Example 5. The dry ethereal solution is distilled (steam bath) and the resuting viscous yellow oil is taken up in 5 ml. of absolute ethanol. To this solution is added 3.49 g. (30 mmoles) of maleic acid dissolved in the minimum amount of absolute alcohol. This product is then diluted with ether prior to the cloud-point and allowed to stand in the cold. The resulting maleate salt is obtained as white crystals. It was recrystallized from absolute alcoholabsolute ether, M.P.'73.8-74.3 C.

Analysis.Calculated for C H F NO (percent): C, 47.3; H, 4.7; F, 21.9; N, 4.6. Found (percent): C, 46.3; H, 4.4; F, 20.4; N, 4.3.

Example 37.Preparation of fi-diethylaminoethyl 1-(2,2, 2-trifiuoroethoxy) -2-naphthoate hydrochloride Anhydrous potassium bicarbonate (5.2 g., 5.2 mmoles),

1-(2,2,2-trifluoroethoxy)-2-naphthoic acid (4.7 g., 17.4 mmoles) and toluene (100 ml.) are refluxed under a water trap with eflicient stirring for 1.5 hours (the theoretical amount of water separated within the first hour). To the cooled product is then added B-diethylaminoethyl chloride hydrochloride and the mixture is refluxed with stirring for one day. The cold material is filtered and the clear filtrate is concentrated to a viscous residue. This residue is taken up in ether and then washed successively with cold dilute aqueous sodium hydroxide and water. The dried ethereal solution is filtered from drying agent (anhydrous magnesium sulfate) and the filtrate is saturated with dry gaseous hydrogen chloride. On standing, white crystals form. They are collected and recrystallized from absolute alcohol-absolute ether, M.P. 124-l25.5 C.

Analysis.Calculated for C H ClF NO (percent): C, 56.2; H, 5.7; F, 14.0; N, 3.4. Found (percent): C, 56.4; H, 6.0; F, 13.9; N, 3.4.

Example 38.Preparation of fl-diethylaminoethyl 1-(1,1- dihydroperfluoroisobutoxy) -2-naphthoate hydrochloride Anhydrous potassium bicarbonate and 1-(1,1-dihydroperfluoroisobutoxy) -2-naphthoic acid in the molar ratio of Y 3 to 1 are refluxed in toluene under a water trap with efiicient stirring for 1.5 hours (the theoretical amount of water separating within the first hour). To the cooled product is then added fl-diethylaminoethyl chloride hydrochloride and the mixture is refluxed with stirring for one day. The cold material is filtered and the clear filtrate is up in ether and then washed successively with cold dilute aqueous sodium hydroxide and water. The dried ethereal solution is filtered from drying agent (anhydrous magnesium sulfate) and the filtrate is saturated with dry gaseous hydrogen chloride. On standing, white crystals of fi-diethylaminoethyl 1-( 1,1-dihydroperfluoroisobutoxy)-2-naphthoate hydrochloride form. They are collected and recrystallized from absolute alcohol-absolute ether. Example 39.-Preparation of p-diethylaminoethyl 2,4,6-

tri-[2,2 difluoro-2-(trifluoromethoxy)ethoxy]benzoate hydrochloride A mixture containing 1 mole of 2,4,6-tri-[2,2-difluoro- 2-(trifluoromethoxy)ethoxylbenzoic acid and 3 moles of anhydrous potassium bicarbonate in toluene iswell-stirred and refluxed under a water trap for two hours (most of 13 the water separates within the first hour of reaction). The material is cooled and to it is added 1 mole of B-diethylaminoethyl chloride hydrochloride. This product is refluxed under a water trap with efficient stirring for one 14 well-stirred and refluxed under a water trap for two hours (most of the water separates within the first hour of reaction). The material is cooled and to it is added 5.16 g. (30 mmoles) of B-diethylaminoethyl chloride hydrochloday. Solvent is removed under diminished pressure and ride. This product is refluxed under a water trap with efthe residue is taken up in an ether-water mixture. The ficient stirring for one day. Solvent is removed under organic layer is separated, Water-washed and dried (andiminished pressure and the residue is taken up in an hydrous magnesium sulfate). The ethereal solution is filether-Water mixture. The organic layer is separated, tered and the filtrate is saturated with anhydrous, gaseous water-washed and dried (anhydrous magnesium sulfate). hydrogen chloride. The resulting white crystals of fl-di- The ethereal solution is filtered and the filtrate is saturated ethylaminoethyl 2,4,6 tr-i-[2,2-difluoro-2-(trifiuoromethwith anhydrous, gaseous hydrogen chloride. The product oxy)-ethoxy]benzoate hydrochloride are collected and is protected from moisture and allowed to stand for one purified by recrystallization from an absolute alcohol-abday. The resulting white crystals are collected and purisolute ether combination. fied by recrystallization from an absolute alcoholabsolute ether combination, M.P. 87-89 C. Example 40.- Preparat1on of fl-diethylannnoethyl 2,4-d1- Analysis calculated for CWHZZCIFGNO4 (percent)2 (2,2,2-tr1fluoroethoxy)-benzoate hydrochloride C, 451}; H, 49; F N, Found (percent): C, A mixture containing 9.55 g. (30 mmoles) of 2,4-di- (2,2 Z-trifluoroethoxy)benzoic acid, 9 g. (90 mmoles) of U anhydrous potassium bicarbonate and 100 ml. of toluene Example 4 2PPreparatlon of fl'dlethylamlnoethyl is well-stirred and refluxed under a water trap for two (zzz'mfluoroethoxy)'z'naphthoate hydrochlonde hOUIS (most Of the water separates Within the first hour Anhydrous potassium bicarbonate (5,2, g, 62,2 Of reaction). The material iS cooled and to it iS added 5.16 mmoles), 3 (2,2,2 trifluoroethoxy)-2-r1aphthoic acid g. (30 moles) of B-diethylaminoethyl chloride hydro- (4.7 g., 17.4 mmoles) and toluene (100 ml.) are refluxed chloride. This product iS refluxed under a water trap With under a water trap with efl'icient stirring for 1,5 hours efficient stirring for one day. Solvent is removed under (the theoretical amount of water separates within the first diminished pressure and the residue is taken up in an h T th l d d t i h dd d gdi h p th miXtllfe- The Organic layer is separated, aminoethyl chloride hydrochloride and the mixture is reter-washed and dried (anhydrous magnesium sulfate). fiuxed with stirring for one day. The cold material is The ethereal solution is filtered and the filtrate is saturated filtered and the clear filtrate is concentrated to a viscous with anhydrous, gaseous hydrogen chloride. The product residue. This residue is taken up in ether and then washed is protected from moisture and allowed to stand for one successively with cold dilute aqueous sodium hydroxide day. The resulting white crystals are collected and puriand water. The dried ethereal solution is filtered from fled by recrystallization from an absolute alcohol-absolute drying agent (anhydrous magnesium sulfate) and the ether combination, M.P. 128l29 C. filtrate is saturated with dry gaseous hydrogen chloride. Analysis.Calo111ated for C H ClF NO (percent): On standing white crystals form. They are collected and C, 45.0; H, 4.9; F, 25.1; N, "3.0. Found (percent): C, 45.1; recrystallized from absolute alcohol-absolute ether, M.P. H, 5.1; F, 26.0; N, 3.1. 142-l43.5 Example 41.--Preparation of p-diethylaminoethyl 2,5-di- 40 C g ig fii i g a f i i ff igfig zg gg ff g (2,2,2-tr1fiuoroethoxy)-benzoate hydrochloride I 561; H, 5.6; F, 14.0; N, 3.3. A mixture containing 9.55 -g. (30 mmoles) of 2,5-d1- Additional compounds of Formula I (as their salts) (2,2,2-trifluoroethoxy)-benzoic acid, 9 g. mmoles) of are prepared according to the procedures described in Exanhydrous potassium bicarbonate and ml. of toluene is amples 35 through 42 and are listed in Table VII.

TABLE VII Starting material Example No. Formula III Formula V Product 43 C(|)OH C1(CHz)iN(CH2CHa)i-HC1 CO|z(OHz)gN(CHzCH;) -H0l CFSCH20- 0CH CFa CFaCHiO OCH2CF l l OCHgCFa OCHzCF:

44 C(|)0H CKCHrhNOSHaCHah-HCI C?2(CH2)2N(CH2CH3)z-HC1 CF CH2O OCH OFa CFaCHzO- OCHzCFa OCH2CF3 jHzcFg 45 $0011 CICHzCH2N(CHa)z-HCl (|JOzCHzCH N(CH -HCI OCHzOFzCF; -0 OHzCFzCF;

46 F0011 CH3 (3H1 C1CHCH2N(CHa)z-HC1 COzCHCHzN(CH3)z-HCI OCH2(CF2)2H l 15 What is claimed is: 1. A compound of the formula:

wherein R and R are alkyl groups of one to three carbon atoms each, eachvQ is hydrogen or a lower alkyl group, Ar is an aryl group containing from six to ten carbon atoms, each Rf is a fluorocarbon group containing from one to three carbon atoms and n is one to four; and pharmaceutically acceptable salts thereof.

2. A compound according to claim 1 wherein n is 1.

3. A compound according to claim 1 wherein n is 2.

4. A compound according to claim 1 wherein each Q is hydrogen and R is trifluoromethyl.

5. A compound of the formula:

wherein R and R are lower alkyl groups of from one to three carbon atoms each and R; is a fluorocarbon group containing from one to three carbon atoms; and pharmaceutically acceptable salts thereof.

6. B Diethylaminoethyl 1 (2,2,2-trifluoroethoxy)-2- naphthoate hydrochloride according to claim 5.

16 7. ,8 Diethylaminoethyl 3 (2,2,2,-trifluoroethoxy)-2- naphthoate hydrochloride according to claim 5.

8. A compound of the formula:

wherein R and R are lower alkyl groups of from one to three carbon atoms each and each R; is a fluorocarbon group containing from one to three carbon atoms; and pharmaceutically acceptable salts thereof.

9. )8 Diethylaminoethyl 2,5-di-(2,2,2-trifluoroethoxy) benzoate hydrochloride according to claim 8.

References Cited FOREIGN PATENTS 412,699 4/1925 Germany 260-521 A LORRAINE A. WEINBERGER, Primary Examiner J. F. TERAPANE, Assistant Examiner US. Cl. X.R. 

